This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-EB-102, Development of biomedical technologies and systems Low molecular weight small molecules and peptides often have limited therapeutic utility because of poor pharmacokinetic profile and rapid clearance. As a result, there has been a large effort focused on the development of drug delivery systems, including using large biomolecules as carrier proteins. Protein carriers offer several substantial advantages over other delivery methods including relatively low off-target activity, resulting in fewer side effects. Many of these carrier proteins are recombinant genetic fusions with a therapeutic peptide of interest. Alternately, chemically elaborating carrier proteins with small molecule drugs or peptides can also render the peptide therapeutic more potent and longer lasting. The optimal benefit of protein chemical modification is achieved when the modification is site-specific. However, none of the existing methods for site-specific protein modification are simple, non-toxic, and applicable to proteins expressed in either mammalian or bacterial cells. As a consequence, peptide therapeutics that could be improved by chemical modification have yet to be optimized in this manner. Redwood Bioscience Inc. has developed a technology platform that allows us to chemically modify proteins in a controlled, site-specific manner. The end result is a protein elaborated at a single point. We believe this technology can be used to generate a carrier protein scaffold for delivery of peptide drugs. This scaffold will be homogenous, easy to chemically elaborate, and result in cost-effective, long-lasting protein conjugate therapies to treat unmet medical needs. If successful, we believe this work will change the utility of protein therapeutics by enabling rapid use of small molecules and peptides that otherwise would not be useful as treatment for disease. Our technology will yield higher quality homogenous protein products, reduced dosage frequency resulting in lower treatment costs, and with higher specific biological activity compared to the free peptide drugs or other conjugation methods currently used in the pharmaceutical industry. The research is to be initially carried out by a team of three chemists and biologists, to be funded through this grant. Successful completion of the aims in this proposal will generate the required scientific data necessary to approach outside private sources of capital. This will allow us to grow the company and further develop our commercial targets and hire additional full time scientific and support staff. Redwood Bioscience's aldehyde-tag technology can be applied to create modified human serum albumin proteins. These proteins will be attached to peptide-based drugs and the resulting conjugates demonstrated to be efficacious, cost-effective therapies for diabetes and osteoporosis.